The invention relates to compounds including dendrimers conjugated to targeting peptides and one or more therapeutic, diagnostic, or imaging agents and uses of such compounds.
The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). The BBB is considered to be the major route for the uptake of serum ligands since its surface area is approximately 5000-fold greater than that of BCSFB. The brain endothelium, which constitutes the BBB, represents the major obstacle for the use of potential drugs against many disorders of the CNS. As a general rule, only small lipophilic molecules may pass across the BBB, i.e., from circulating systemic blood to brain. Many drugs that have a larger size or higher hydrophobicity show promising results in animal studies for treating CNS disorders. Thus, peptide and protein agents such as those used as therapeutics are generally excluded from transport from blood to brain, owing to the negligible permeability of the brain capillary endothelial wall to these agents.
Therapy of brain diseases can be impaired by the inability of otherwise effective agents such as therapeutic agents to cross the BBB. Thus, new strategies for transporting agents into the brain with high efficiency are desired.